Therapeutic agents may be administered either systemically or locally. Systemic delivery involves the administration of a therapeutic agent at a discrete location followed by the dispersal of the agent throughout the patient's body including, of course, to the target treatment site or organ. In order to achieve a therapeutically effective amount of the agent at the afflicted site, it is usually necessary to administer an initial dose substantially greater than the therapeutically effective amount to account for the dilution the agent undergoes as it travels through the body. Systemic delivery is carried out primarily in two ways: introduction of the therapeutic agent into the digestive tract (enteral administration) or into the vascular system (parenteral administration), either directly such as injection into a vein or an artery or indirectly such as injection into a muscle or into the bone marrow. Delivery by each of these routes is strongly influenced by the so-called ADMET factors: absorption, distribution, metabolism, excretion and toxicity. For enteric administration, such factors as a compound's solubility, its stability in the acidic environs of the stomach and its ability to permeate the intestinal wall all affect the extent to which the drug is absorbed and therefore its bioavailability. For parenteral delivery factors such as enzymatic degradation, the lipophilic/hydrophilic partitioning coefficient, protein binding, etc. will affect the bioavailability of an agent.
Local delivery comprises administration of the therapeutic agent directly to the target site. The ADMET factors tend to be less important than with systemic administration since the agent is being administered essentially directly to the treatment site. Thus, the initial dose can be at or very close to the therapeutically effective amount. This permits a more economic use of therapeutic agent. Further, since administration is local, a lower therapeutic index can be tolerated without adverse side effects. In fact, the benefits of local delivery over systemic delivery militate in favor of the former if the disease being treated is localized to a specific organ or tissue.
A current means of local delivery of therapeutic agents for the treatment of vascular disease is use of a drug-eluting stent (DES). A stent is coated with a drug-containing polymer, inserted into a patient's vessel, advanced to the diseased locale and deposited there. The drug then elutes from the stent and performs its therapeutic function. This approach is appropriate for diseased tissues that are accessible to fairly large, physiologically speaking, stents. Many tissue locales, however, are not so conveniently located and the afflicted region may be well away from the nearest vessel amenable to stenting. Thus, while the use of a drug-coated stent would still bring the therapeutic agent closer to the afflicted area than could be achieved by systemic delivery, delivery of the therapeutic agent would still depend on passive diffusion to reach the diseased tissue.
What would be beneficial is a method of getting substantially closer to the diseased regions of a tissue and to be able to control to some extent the diffusion of the drug in the diseased tissue. The current invention provides such a method.